TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling.
TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling.
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TLR4和CD14的运输及其对LPS诱导的促炎信号传导的影响
DOI：
10.1007/s00018-020-03656-y
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Kwiatkowska K
中科院分区：
文献类型：
--
作者：
Ciesielska A;Matyjek M;Kwiatkowska K
Toll样受体（TLR）4属于诱导对入侵病原体的促炎反应的TLR受体家族。TLR 4被革兰氏阴性菌的脂多糖（LPS，内毒素）激活，并依次触发两个信号级联：第一个涉及TIRAP和MyD 88衔接蛋白在质膜中诱导，而第二个衔接衔接蛋白TRAM和TRIF在受体的内吞作用后的早期内体中开始。LPS诱导的TLR 4内化以及因此TRIF依赖性途径的激活由GPI锚定蛋白CD 14控制。TLR 4的内吞作用终止了MyD 88依赖性信号传导，而随后的内体成熟和TLR 4的溶酶体降解决定了TRIF依赖性信号传导的持续时间和幅度。或者，TLR 4可能会返回质膜，这一过程仍然知之甚少。因此，LPS诱导的促炎反应的过程严格依赖于TLR 4内吞和通过内-溶酶体区室的运输速率。值得注意的是，TLR 4的长期激活与几种遗传性人类疾病、神经变性以及自身免疫性疾病和癌症有关。最近的研究提供了大量的数据，在TLR 4诱导的炎症反应中，不同的蛋白质调节早期、晚期和再循环内体的功能，这些炎症反应由LPS或E.杆菌在这篇综述中，我们专注于TLR 4和CD 14的内化和细胞内运输的机制，也LPS，在免疫细胞中，并讨论如何失调的内溶酶体室有助于发展的各种人类疾病。
Toll-like receptor (TLR) 4 belongs to the TLR family of receptors inducing pro-inflammatory responses to invading pathogens. TLR4 is activated by lipopolysaccharide (LPS, endotoxin) of Gram-negative bacteria and sequentially triggers two signaling cascades: the first one involving TIRAP and MyD88 adaptor proteins is induced in the plasma membrane, whereas the second engaging adaptor proteins TRAM and TRIF begins in early endosomes after endocytosis of the receptor. The LPS-induced internalization of TLR4 and hence also the activation of the TRIF-dependent pathway is governed by a GPI-anchored protein, CD14. The endocytosis of TLR4 terminates the MyD88-dependent signaling, while the following endosome maturation and lysosomal degradation of TLR4 determine the duration and magnitude of the TRIF-dependent one. Alternatively, TLR4 may return to the plasma membrane, which process is still poorly understood. Therefore, the course of the LPS-induced pro-inflammatory responses depends strictly on the rates of TLR4 endocytosis and trafficking through the endo-lysosomal compartment. Notably, prolonged activation of TLR4 is linked with several hereditary human diseases, neurodegeneration and also with autoimmune diseases and cancer. Recent studies have provided ample data on the role of diverse proteins regulating the functions of early, late, and recycling endosomes in the TLR4-induced inflammation caused by LPS or phagocytosis of E. coli. In this review, we focus on the mechanisms of the internalization and intracellular trafficking of TLR4 and CD14, and also of LPS, in immune cells and discuss how dysregulation of the endo-lysosomal compartment contributes to the development of diverse human diseases.
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影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
影响因子：
4.8
作者：
Chiang, Chih-Yuan;Veckman, Ville;David, Michael
通讯作者：
David, Michael
早期神经变性与硫酸乙酰肝素在粘多糖糖化IIIB小鼠大脑中的小胶质细胞激活无关。
影响因子：
3.7
作者：
Ausseil, Jerome;Desmaris, Nathalie;Bigou, Stephanie;Attali, Ruben;Corbineau, Sebastien;Vitry, Sandrine;Parent, Mathieu;Cheillan, David;Fuller, Maria;Maire, Irene;Vanier, Marie-Therese;Heard, Jean-Michel
通讯作者：
Heard, Jean-Michel
影响因子：
16.6
作者：
Banushi B;Forneris F;Straatman-Iwanowska A;Strange A;Lyne AM;Rogerson C;Burden JJ;Heywood WE;Hanley J;Doykov I;Straatman KR;Smith H;Bem D;Kriston-Vizi J;Ariceta G;Risteli M;Wang C;Ardill RE;Zaniew M;Latka-Grot J;Waddington SN;Howe SJ;Ferraro F;Gjinovci A;Lawrence S;Marsh M;Girolami M;Bozec L;Mills K;Gissen P
通讯作者：
Gissen P
影响因子：
29.7
作者：
Brubaker SW;Bonham KS;Zanoni I;Kagan JC
通讯作者：
Kagan JC